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Quantum-chemical investigation on 5-fluorouracil anticancer drug

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Abstract

DFT with B3LYP/6-311++G(d,p) level were used for all calculations in this work. In biological system, 5-FU-3H2O has the highest stabilization energy compared to 5-FU-3NH3, 5-FU dimer, and 5-FU monomer. The chemical interactions of 2′-deoxyribose radical with uracil and 5-FU radicals to form 2′-deoxyuridine and 2′-deoxy-5-fluorouridine show that the difference in stabilization energies, ΔE, for their formation are quite low which facilitates the exchange reactions in DNA structure. Size, shape density distributions, and chemical reactivity sites of 5-FU were obtained by mapping electron density isosurface with electronic surface. Additionally, the intermolecular hydrogen bonding in 5-FU (sugar-phosphate) backbone system was simulated by NBO analysis to describe the role of intermolecular hydrogen bonding on the structure and chemical reactivity of 5-FU in biological systems. Molecular docking study of the interaction between 5-FU and human serum albumin (HSA) indicated that 5-FU binds to HSA with low affinity and low specificity compared to other anticancer drugs.

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Physics Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt

    Hala Sh. Mohamed & Galal S. Hassan

  2. Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt

    AbdelRahman A. Dahy & Refaat M. Mahfouz

  3. Department of Clinical Oncology and Nuclear Medicine, Assiut university hospitals, Faculty of Medicine, Assiut University, Assiut, 71526, Egypt

    Samir-Shehata M. Eid

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  1. Hala Sh. Mohamed
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  2. AbdelRahman A. Dahy
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  3. Galal S. Hassan
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Correspondence to Refaat M. Mahfouz.

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Mohamed, H.S., Dahy, A.A., Hassan, G.S. et al. Quantum-chemical investigation on 5-fluorouracil anticancer drug. Struct Chem 28, 1093–1109 (2017). https://doi.org/10.1007/s11224-017-0913-3

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